Irritability emerges during infancy and is a substrate of many common forms of developmental psychopathology. However, reliable identification of irritable infants at high risk for clinical progression is challenging due to high levels of normatve variation combined with substantial individual differences in adaptive or maladaptive outcomes for irritable infants over time. Building on our prior work at preschool age, the proposed study utilizes a neurodevelopmental framework to generate empirically derived, parameters for differentiation of irritability patterns that mark risk for clinical progression. Key innovations ae: (1) novel approach to specification of developmentally atypical patterns of irritability beginning n infancy; (2) joint developmental consideration of irritability, executive function, and prefrontal cortical regions; and (3) transactional focus examining the clinical import of early irritability wthin the context of parent-infant mutual (dys)regulation. To derive population-based parameters, we first conduct a cross-sectional survey of a representative sample of 12-36 mos. olds (N=2,000). We then ascertain an independent community cohort (N=350 infants oversampled for irritability), with intensive longitudinal follow-up from 12-36 months. Focal irritability assessments are: (a) bimonthly parent reports and real-time monitoring of irritable vocalizations via the Language Environment Analysis (LENA) Pro device; and (b) annual direct observations of irritable temperament and behavior (12, 24 & 36 mos.). Performance-based assessments of executive function occur annually. Transactional processes are assessed via parental contingent responses to infant irritable vocalizations on the LENA Pro (bimonthly) and event-coded parent-infant mutual regulation processes (annually). Clinical progression is captured via latent dimensional clinical risk over time. SPECIFIC AIMS: IA. Differentiate developmentally atypical irritability patterns from infancy-early preschool age via population-based parameters cross-sectionally (IAi) and quantitative longitudinal parameters (IAii). IB. Specify longitudinal parameters of irritability to optimize prediction of clinical progression. IIA-B. Map developmentally atypical irritability patterns to disruptions in the maturation of executive functin and prefrontal cortical (PFC) regions and test the hypothesis that their joint consideration will enhance predictive clinical utility. Prefrontal cortical maturation will be assessed from infant natural sleep-MRI derived estimates of anatomical properties at 12 & 36 months in an extreme group sub-sample (n=100). We test the hypothesis that atypical irritability patterns will predict slowed executive function development and abnormal PFC anatomy. IIIA-B. Elucidate how transactional processes shape clinical prediction, testing the hypothesis that parent-infant mutual regulation processes modulate clinical progression. Specification of neurodevelopmental irritability phenotypes within transactional context provides a critical empirical base for targete prevention of mental disorder in its earliest prodromal phases.